tbuckley/cabot-search huggingface dataset:
Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs
Authors: Maximiliane Chiara Hammel, Robert Stein, Jürgen Kratzsch, Mandy Vogel, Alexander J. Eckert, Rima Destya Triatin, Marco Colombo, Christof Meigen, Ronny Baber, Juraj Stanik, Ulrike Spielau, Anette Stoltze, Kerstin Wirkner, Anke Tönjes, Harold Snieder, Reinhard W. Holl, Michael Stumvoll, Matthias Blüher, Wieland Kiess, Antje Körner
Journal: The Lancet Regional Health - Europe (2023)

Fasting indices of glucose-insulin-metabolism are an easy and affordable tool to assess insulin resistance. We aimed to establish reference ranges for fasting insulin indices that reflect age-dependent variation over the entire life span and subsequently test their clinical application regarding the prediction of glycemic deterioration in children. We calculated age- and puberty-dependent reference values for HOMA-IR, HOMA2-IR, HOMA-β, McAuley index, fasting insulin, and fasting glucose from 6994 observations of 5512 non-obese healthy subjects aged 5–80 years. Applying those references, we determined the prevalence of insulin resistance among 2538 subjects with obesity. Furthermore, we investigated the intraindividual stability and the predictive values for future dysglycemia of these fasting indices in 516 children and adolescents with obesity up to 19 years of follow-up. We validated the results in three independent cohorts. There was a strong age-dependent variation of all indices throughout the life span, including prolonged recovery of pubertal insulin resistance and a subsequent continuous increase throughout adulthood. Already from age 5 years onwards, >40% of children with obesity presented with elevated parameters of insulin resistance. Applying newly developed reference ranges, insulin resistance among children with obesity doubled the risk for future glycemic deterioration (HOMA-IR HR 1.88 (95% CI 1.1–3.21)), fasting insulin HR 1.89 (95% CI 1.11–3.23). In contrast, fasting glucose alone was not predictive for emerging dysglycemia in children with obesity (HR 1.03 (95% CI 0.62–1.71)). The new insulin-based thresholds were superior to fasting glucose and HbA1c in detecting children eventually manifesting with dysglycemia in prospective analyses. The variation of fasting glucose-insulin-metabolism across the life span necessitates age-specific reference ranges. The improved prediction of future glycemic deterioration by indices based on fasting insulin beyond simple glucose measures alone could help to stratify risk characteristics of children with obesity in order to guide patient-tailored prevention and intervention approaches. German Research Foundation (DFG)—through SFB 1052, project number 209933838, subproject C5; Federal Ministry of Education and Research, Germany; European Union–European Regional Development Fund; Free State of Saxony. The German Diabetes Association, the CarbHealth consortium (01EA1908B). EU-IMI2-Consortium SOPHIA (grant agreement No 875534), German Center for Diabetes Research (DZD), grant number 82DZD14E03.
Integrating non-communicable disease prevention and control into maternal and child health programmes
Authors: Suzanne M Simkovich, Megan E Foeller, Özge Tunçalp, Aris Papageorghiou, William Checkley
Journal: BMJ (2023)

<b>Suzanne Simkovich and colleagues</b> argue for implementation research to meet the needs of end users and use of open source data to strengthen preventive strategies for non-communicable diseases in women of reproductive age
Acute heart failure and valvular heart disease: A scientific statement of the Heart Failure Association, the Association for Acute <scp>CardioVascular</scp> Care and the European Association of Percutaneous Cardiovascular Interventions of the European Society of Cardiology
Authors: Ovidiu Chioncel, Marianna Adamo, Maria Nikolaou, John Parissis, Alexandre Mebazaa, Mehmet Birhan Yilmaz, Christian Hassager, Brenda Moura, Johann Bauersachs, Veli‐Pekka Harjola, Elena‐Laura Antohi, Tuvia Ben‐Gal, Sean P. Collins, Vlad Anton Iliescu, Magdy Abdelhamid, Jelena Čelutkienė, Stamatis Adamopoulos, Lars H. Lund, Mariantonietta Cicoira, Josep Masip, Hadi Skouri, Finn Gustafsson, Amina Rakisheva, Ingo Ahrens, Andrea Mortara, Ewa A. Janowska, Abdallah Almaghraby, Kevin Damman, Oscar Miro, Kurt Huber, Arsen Ristic, Loreena Hill, Wilfried Mullens, Alaide Chieffo, Jozef Bartunek, Pasquale Paolisso, Antoni Bayes‐Genis, Stefan D. Anker, Susanna Price, Gerasimos Filippatos, Frank Ruschitzka, Petar Seferovic, Rafael Vidal‐Perez, Alec Vahanian, Marco Metra, Theresa A. McDonagh, Emanuele Barbato, Andrew J.S. Coats, Giuseppe M.C. Rosano
Journal: European Journal of Heart Failure (2023)
With sexual harassment or assault, what you permit, you promote
Authors: Simon Fleming
Journal: BMJ (2023)

With sexual harassment or assault, what you permit, you promoteIt is everyone's responsibility to hold sexual predators in the NHS accountable or risk becoming complicit bystanders, writes Simon Fleming Simon Fleming orthopaedic surgeonGrowing evidence shows that healthcare in the United Kingdom and worldwide has a problem with sexual violence.Increasing numbers of people who have faced sexual violence, predominantly women, are coming forward to share their experiences.
Adverse outcomes of SARS-CoV-2 infection with delta and omicron variants in vaccinated versus unvaccinated US veterans: retrospective cohort study
Authors: Amy SB Bohnert, Kyle Kumbier, Mazhgan Rowneki, Ashwin Gupta, Kristina Bajema, Denise M Hynes, Elizabeth Viglianti, Ann M O’Hare, Thomas Osborne, Edward J Boyko, Yinong Young-Xu, Theodore J Iwashyna, Matthew Maciejewski, Richard Schildhouse, Derek Dimcheff, George N Ioannou
Journal: BMJ (2023)

To determine the association between covid-19 vaccination types and doses with adverse outcomes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the periods of delta (B.1.617.2) and omicron (B.1.1.529) variant predominance. Retrospective cohort. US Veterans Affairs healthcare system. Adults (≥18 years) who are affiliated to Veterans Affairs with a first documented SARS-CoV-2 infection during the periods of delta (1 July-30 November 2021) or omicron (1 January-30 June 2022) variant predominance. The combined cohorts had a mean age of 59.4 (standard deviation 16.3) and 87% were male. Covid-19 vaccination with mRNA vaccines (BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)) and adenovirus vector vaccine (Ad26.COV2.S (Janssen/Johnson & Johnson)). Stay in hospital, intensive care unit admission, use of ventilation, and mortality measured 30 days after a positive test result for SARS-CoV-2. In the delta period, 95 336 patients had infections with 47.6% having at least one vaccine dose, compared with 184 653 patients in the omicron period, with 72.6% vaccinated. After adjustment for patient demographic and clinical characteristics, in the delta period, two doses of the mRNA vaccines were associated with lower odds of hospital admission (adjusted odds ratio 0.41 (95% confidence interval 0.39 to 0.43)), intensive care unit admission (0.33 (0.31 to 0.36)), ventilation (0.27 (0.24 to 0.30)), and death (0.21 (0.19 to 0.23)), compared with no vaccination. In the omicron period, receipt of two mRNA doses were associated with lower odds of hospital admission (0.60 (0.57 to 0.63)), intensive care unit admission (0.57 (0.53 to 0.62)), ventilation (0.59 (0.51 to 0.67)), and death (0.43 (0.39 to 0.48)). Additionally, a third mRNA dose was associated with lower odds of all outcomes compared with two doses: hospital admission (0.65 (0.63 to 0.69)), intensive care unit admission (0.65 (0.59 to 0.70)), ventilation (0.70 (0.61 to 0.80)), and death (0.51 (0.46 to 0.57)). The Ad26.COV2.S vaccination was associated with better outcomes relative to no vaccination, but higher odds of hospital stay and intensive care unit admission than with two mRNA doses. BNT162b2 was generally associated with worse outcomes than mRNA-1273 (adjusted odds ratios between 0.97 and 1.42). In veterans with recent healthcare use and high occurrence of multimorbidity, vaccination was robustly associated with lower odds of 30 day morbidity and mortality compared with no vaccination among patients infected with covid-19. The vaccination type and number of doses had a significant association with outcomes.
Revive and Refuse: Capacity, Autonomy, and Refusal of Care After Opioid Overdose
Authors: Kenneth D. Marshall, Arthur R. Derse, Scott G. Weiner, Joshua W. Joseph
Journal: The American Journal of Bioethics (2023)

Physicians generally recommend that patients resuscitated with naloxone after opioid overdose stay in the emergency department for a period of observation in order to prevent harm from delayed sequelae of opioid toxicity. Patients frequently refuse this period of observation despiteenefit to risk. Healthcare providers are thus confronted with the challenge of how best to protect the patient's interests while also respecting autonomy, including assessing whether the patient is making an autonomous choice to refuse care. Previous studies have shown that physicians have widely divergent approaches to navigating these conflicts. This paper reviews what is known about the effects of opioid use disorder on decision-making, and argues that some subset of these refusals are non-autonomous choices, even when patients appear to have decision making capacity. This conclusion has several implications for how physicians assess and respond to patients refusing medical recommendations after naloxone resuscitation.
FDA advisers back Pfizer’s maternal RSV vaccine after voicing safety concerns
Authors: Hristio Boytchev
Journal: BMJ (2023)

FDA advisers back Pfizer's maternal RSV vaccine after voicing safety concerns Hristio BoytchevWhether Pfizer's maternal respiratory syncytial virus (RSV) vaccine candidate increases the risk of preterm birth dominated discussions at a meeting last week of the committee advising the US Food and Drug Administration (FDA). 1 While all members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted positively on efficacy, four out of 14 voted that the data were not adequate to support safety.As The BMJ revealed earlier this month, 2 Pfizer's clinical trials showed increased levels of preterm births among vaccinated women, and GSK, which was working on a similar vaccine, halted vaccination in its phase 3 trials after observing an increase in neonatal deaths and preterm births. 3 4
Bounded Justice, Inclusion, and the Hyper/Invisibility of Race in Precision Medicine
Authors: Kadija Ferryman
Journal: The American Journal of Bioethics (2023)

I take up the call for a more nuanced engagement with race in bioethics by using Creary's analytic of bounded justice and argue that it helps illuminate processes of racialization, or racial formation, specifically Blackness, as a dialectical processes of both invisibility and hyper-visibility. This dialectical view of race provides a lens through which the ethical, legal, and social implications (ELSI) of genetics and genomics field can reflect on fraught issues such as inclusion in genomic and biomedical research. Countering or interrupting racialization in precision medicine can involve asking how marginalized groups are made invisible or hyper-visible in various aspects of the research process. Incorporating these kinds of questions into biomedical research inclusion efforts could lead to potentially powerful engagements with marginalized groups and could provide the opportunity for stakeholders to engage with the ways that racialization can happen in real-time and might undermine good intentions.
Patient-centered, self-funding dose optimization trials as a route to reduce toxicity, lower cost, and improve access to cancer therapy
Authors: I.F. Tannock, G. Bouche, D.A. Goldstein, Y. Goto, A.S. Lichter, K. Prabhash, P. Ranganathan, L.B. Saltz, G.S. Sonke, G.W. Strohbehn, R. von Moos, M.J. Ratain
Journal: Annals of Oncology (2023)
A wave of deep intronic mutations in X-linked Alport syndrome
Authors: Marie Boisson, Christelle Arrondel, Nicolas Cagnard, Vincent Morinière, Zaïna Aït Arkoub, Hassan Saei, Laurence Heidet, Jessica Kachmar, Aurélie Hummel, Bertrand Knebelmann, Marie-Noëlle Bonnet-Dupeyron, Bertrand Isidor, Hassane Izzedine, Eric Legrand, Philippe Couarch, Olivier Gribouval, Christine Bole-Feysot, Mélanie Parisot, Patrick Nitschké, Corinne Antignac, Guillaume Dorval
Journal: Kidney International (2023)

X-linked Alport syndrome (XLAS) is an inherited kidney disease caused exclusively by pathogenic variants in the COL4A5 gene. In 10-20% of cases, DNA sequencing of COL4A5 exons or flanking regions cannot identify molecular causes. Here, our objective was to use a transcriptomic approach to identify causative events in a group of 19 patients with XLAS without identified mutation by Alport gene panel sequencing. Bulk RNAseq and/or targeted RNAseq using a capture panel of kidney genes was performed. Alternative splicing events were compared to those of 15 controls by a developed bioinformatic score. When using targeted RNAseq, COL4A5 coverage was found to be 23-fold higher than with bulk RNASeq and revealed 30 significant alternative splicing events in 17 of the 19 patients. After computational scoring, a pathogenic transcript was found in all patients. A causative variant affecting COL4A5 splicing and absent in the general population was identified in all cases. Altogether, we developed a simple and robust method for identification of aberrant transcripts due to pathogenic deep-intronic COL4A5 variants. Thus, these variants, potentially targetable by specific antisense oligonucleotide therapies, were found in a high percentage of patients with XLAS in whom pathogenic variants were missed by conventional DNA sequencing.
Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD
Authors: Se-Hyung Park, Robert N. Helsley, Taghreed Fadhul, Jennifer L.S. Willoughby, Leila Noetzli, Ho-Chou Tu, Marie H. Solheim, Shiho Fujisaka, Hui Pan, Jonathan M. Dreyfuss, Joanna Bons, Jacob Rose, Christina D. King, Birgit Schilling, Aldons J. Lusis, Calvin Pan, Manoj Gupta, Rohit N. Kulkarni, Kevin Fitzgerald, Philip A. Kern, Senad Divanovic, C. Ronald Kahn, Samir Softic
Journal: Metabolism (2023)
Reprogramming of rhythmic liver metabolism by intestinal clock
Authors: Min Chen, Yanke Lin, Yongkang Dang, Yifei Xiao, Fugui Zhang, Guanghui Sun, Xuejun Jiang, Li Zhang, Jianhao Du, Shuyi Duan, Xiaojian Zhang, Zifei Qin, Jing Yang, Kaisheng Liu, Baojian Wu
Journal: Journal of Hepatology (2023)
Automatic brain MRI motion artifact detection based on end-to-end deep learning is similarly effective as traditional machine learning trained on image quality metrics
Authors: Pál Vakli, Béla Weiss, János Szalma, Péter Barsi, István Gyuricza, Péter Kemenczky, Eszter Somogyi, Ádám Nárai, Viktor Gál, Petra Hermann, Zoltán Vidnyánszky
Journal: Medical Image Analysis (2023)

Head motion artifacts in magnetic resonance imaging (MRI) are an important confounding factor concerning brain research as well as clinical practice. For this reason, several machine learning-based methods have been developed for the automatic quality control of structural MRI scans. Deep learning offers a promising solution to this problem, however, given its data-hungry nature and the scarcity of expert-annotated datasets, its advantage over traditional machine learning methods in identifying motion-corrupted brain scans is yet to be determined. In the present study, we investigated the relative advantage of the two methods in structural MRI quality control. To this end, we collected publicly available T1-weighted images and scanned subjects in our own lab under conventional and active head motion conditions. The quality of the images was rated by a team of radiologists from the point of view of clinical diagnostic use. We present a relatively simple, lightweight 3D convolutional neural network trained in an end-to-end manner that achieved a test set (N = 411) balanced accuracy of 94.41% in classifying brain scans into clinically usable or unusable categories. A support vector machine trained on image quality metrics achieved a balanced accuracy of 88.44% on the same test set. Statistical comparison of the two models yielded no significant difference in terms of confusion matrices, error rates, or receiver operating characteristic curves. Our results suggest that these machine learning methods are similarly effective in identifying severe motion artifacts in brain MRI scans, and underline the efficacy of end-to-end deep learning-based systems in brain MRI quality control, allowing the rapid evaluation of diagnostic utility without the need for elaborate image pre-processing.
The role of early defervescence in ruling out infective endocarditis: a cohort study
Authors: Elisavet Stavropoulou, Benoit Guery, Nicoleta Ianculescu, Piergiorgio Tozzi, Matthias Kirsch, Pierre Monney, Matthaios Papadimitriou-Olivgeris
Journal: Clinical Microbiology and Infection (2023)
Quality of inpatient paediatric and newborn care in district hospitals: WHO indicators, measurement, and improvement
Authors: Mike English, Jalemba Aluvaala, Michuki Maina, Trevor Duke, Grace Irimu
Journal: The Lancet Global Health (2023)

Poor-quality paediatric and neonatal care in district hospitals in low-income and middle-income countries (LMICs) was first highlighted more than 20 years ago. WHO recently developed more than 1000 paediatric and neonatal quality indicators for hospitals. Prioritising these indicators should account for the challenges in producing reliable process and outcome data in these settings, and their measurement should not unduly narrow the focus of global and national actors to reports of measured indicators. A three-tier, long-term strategy for the improvement of paedicatric and neonatal care in LMIC district hospitals is needed, comprising quality measurement, governance, and front-line support. Measurement should be better supported by integrating data from routine information systems to reduce the future cost of surveys. Governance and quality management processes need to address system-wide issues and develop supportive institutional norms and organisational culture. This strategy requires governments, regulators, professions, training institutions, and others to engage beyond the initial consultation on indicator selection, and to tackle the pervasive constraints that undermine the quality of district hospital care. Institutional development must be combined with direct support to hospitals. Too often the focus of indicator measurement as an improvement strategy is on reporting up to regional or national managers, but not on providing support down to hospitals to attain quality care.
Performance and accuracy evaluation of reference panels for genotype imputation in sub-Saharan African populations
Authors: Dhriti Sengupta, Gerrit Botha, Ayton Meintjes, Mamana Mbiyavanga, Scott Hazelhurst, Nicola Mulder, Michèle Ramsay, Ananyo Choudhury
Journal: Cell Genomics (2023)

Based on evaluations of imputation performed on a genotype dataset consisting of about 11,000 sub-Saharan African (SSA) participants, we show Trans-Omics for Precision Medicine (TOPMed) and the African Genome Resource (AGR) to be currently the best panels for imputing SSA datasets. We report notable differences in the number of single-nucleotide polymorphisms (SNPs) that are imputed by different panels in datasets from East, West, and South Africa. Comparisons with a subset of 95 SSA high-coverage whole-genome sequences (WGSs) show that despite being about 20-fold smaller, the AGR imputed dataset has higher concordance with the WGSs. Moreover, the level of concordance between imputed and WGS datasets was strongly influenced by the extent of Khoe-San ancestry in a genome, highlighting the need for integration of not only geographically but also ancestrally diverse WGS data in reference panels for further improvement in imputation of SSA datasets. Approaches that integrate imputed data from different panels could also lead to better imputation.
Activity-dependent membrane sculpting deficits in TAOK1-linked neurodevelopmental disease
Authors: Marisol Sampedro-Castañeda, Sila K. Ultanir
Journal: Trends in Neurosciences (2023)

<h2>Abstract</h2> A recent study by Beeman et al. exploring disease-related missense mutations in TAOK1 revealed a self-regulating association of the kinase with the plasma membrane that is critical for neuronal morphogenesis. Using a combination of <i>in vitro</i> approaches and elegant <i>in silico</i> modeling, the authors describe an aberrant membrane protrusions phenotype in kinase-deficient mutants reminiscent of TAOK2's indirect regulation of neuronal morphology, thus providing a converging patho-mechanism across several neurodevelopmental disorders.
Tumor biology and immune infiltration define primary liver cancer subsets linked to overall survival after immunotherapy
Authors: Anuradha Budhu, Erica C. Pehrsson, Aiwu He, Lipika Goyal, Robin Kate Kelley, Hien Dang, Changqing Xie, Cecilia Monge, Mayank Tandon, Lichun Ma, Mahler Revsine, Laura Kuhlman, Karen Zhang, Islam Baiev, Ryan Lamm, Keyur Patel, David E. Kleiner, Stephen M. Hewitt, Bao Tran, Jyoti Shetty, Xiaolin Wu, Yongmei Zhao, Tsai-Wei Shen, Sulbha Choudhari, Yuliya Kriga, Kris Ylaya, Andrew C. Warner, Elijah F. Edmondson, Marshonna Forgues, Tim F. Greten, Xin Wei Wang
Journal: Cell Reports Medicine (2023)

Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field. In a retrospective arm of the National Cancer Institute Cancers of the Liver: Accelerating Research of Immunotherapy by a Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples to profile the transcriptome and genomic alterations among 86 hepatocellular carcinoma and cholangiocarcinoma patients prior to and following immune checkpoint inhibitor treatment. Using supervised and unsupervised approaches, we identify stable molecular subtypes linked to overall survival and distinguished by two axes of aggressive tumor biology and microenvironmental features. Moreover, molecular responses to immune checkpoint inhibitor treatment differ between subtypes. Thus, patients with heterogeneous liver cancer may be stratified by molecular status indicative of treatment response to immune checkpoint inhibitors.